The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures

摘要: Limited distribution of anticancer drugs has been recognized as a significant hurdle to efficacy. We investigated detailed penetration/distribution profile paclitaxel-rhodamine (PTX-rd) and doxorubicin (DOX) in multicellular layer (MCL) cultures human cancer cells an vitro model for avascular regions solid tumors. MCLs were exposed fluorescent images frozen sections acquired determination drug penetration into MCL under various exposure conditions. PTX-rd DOX showed drastically different profiles penetration. full after 1 h accumulation over 3 h, whereas slow limited penetration, with only within the top 20% layers by 2 insignificant even at 72 h. Drug retention was more dependent on concentration, rather than time, i.e., increased 6.3- 2.5-fold DOX, respectively, when higher concentrations comparable AUC (1 μM × 24 vs. 50 0.5 h). Anti-proliferative activity PTX MCL, determined cell cycle analysis, minimal may be attributed, least part, their cultures. Overall, we demonstrated that not concentration- time-dependent, but also schedule-dependent. It is suggested releasing formulations or infusion regimen necessarily desirable, especially PTX, due insufficient which result from low local concentration target site.